The nucleoporin ALADIN regulates Aurora A localization to ensure robust mitotic spindle formation

  • Mol Biol Cell. 2015 Oct 1;26(19):3424-38. doi: 10.1091/mbc.E15-02-0113.
Sara Carvalhal  1 ,  Susana Abreu Ribeiro  2 ,  Miguel Arocena  1 ,  Taciana Kasciukovic  1 ,  Achim Temme  3 ,  Katrin Koehler  4 ,  Angela Huebner  4 ,  Eric R Griffis  5
Affiliations
  • 1. Centre for Gene Regulation and Expression, University of Dundee, College of Life Sciences, Dundee DD1 5EH, United Kingdom.
  • 2. Physiology Course, Marine Biological Laboratory, Woods Hole, MA 02543 Wellcome Trust Centre for Cell Biology, Institute of Cell and Molecular Biology, University of Edinburgh, Edinburgh EH9 3JR, United Kingdom.
  • 3. Department of Neurosurgery, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
  • 4. Department of Paediatrics, University Hospital Carl Gustav Carus, Technische Universität Dresden, D-01307 Dresden, Germany.
  • 5. Centre for Gene Regulation and Expression, University of Dundee, College of Life Sciences, Dundee DD1 5EH, United Kingdom Physiology Course, Marine Biological Laboratory, Woods Hole, MA 02543 [email protected].
PMID: 26246606 DOI: 10.1091/mbc.E15-02-0113
Abstract

The formation of the mitotic spindle is a complex process that requires massive cellular reorganization. Regulation by mitotic kinases controls this entire process. One of these mitotic controllers is Aurora A kinase, which is itself highly regulated. In this study, we show that the nuclear pore protein ALADIN is a novel spatial regulator of Aurora A. Without ALADIN, Aurora A spreads from centrosomes onto spindle microtubules, which affects the distribution of a subset of microtubule regulators and slows spindle assembly and chromosome alignment. ALADIN interacts with inactive Aurora A and is recruited to the spindle pole after Aurora A inhibition. Of interest, mutations in ALADIN cause triple A syndrome. We find that some of the mitotic phenotypes that we observe after ALADIN depletion also occur in cells from triple A syndrome patients, which raises the possibility that mitotic errors may underlie part of the etiology of this syndrome.